This project is designed to apply newly-developed knowledge in cell biology and endocrinology to the study of aging. In the last few years, it has become apparent that the components of serum required for the growth of cells in tissue culture are similar if not identical to the somatomedins, a recently recognized family of hormones which mediate many of the actions of pituitary growth hormone. Many of the tissues (muscle, cartilage, liver) and processes (protein and nucleic acid synthesis, cell division) which show age-related deterioration are those known to be stimulated or maintained by growth hormone, the somatomedins, and related factors. Combining these observations, I suggest that some aspects of aging may result from a decrease in level, induction, or effect on target tissues of the somatomedins and closely related growth-promoting factors. I propose to test this hypothesis by measuring levels of these agents (using myoblast and fibroblast cell growth assays) in serum samples from disease-free Fisher 344 rats at a series of ages throughout their lifespan. After determining these levels in normal untreated animals, I will then measure the effect of age on rate and extent of elevation of the levels following administration of growth hormone in vivo. Diaphragm muscles from untreated rats of the same age will be used to measure age-related changes in sensitivity of amino acid uptake to somatomedin. Finally, release of these hormones from isolated perfused livers and kidneys in response to growth hormone will be measured as a function of age of donor rats. The experiments will provide the first evaluation of the role in aging of a newly recognized family of hormones, and may thus indicate new possibilities for the treatment of some kinds of senile deterioration. In addition, comparison of our results with parallel studies on insulin will be important because of the insulin-like actions of the somatomedins.